title: KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries.
abstract: OBJECTIVE
  Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca(2+) concentration ([Ca(2+)](i)) by opening of K channels and release of H₂S.
  
  
  METHODS
  Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca(2+)](i), and the expression of voltage-gated K channels K(V)7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels (K(Ca)1.1) was examined. Voltage clamp assessed the role of K(V)7 channels in hypoxia.
  
  
  RESULTS
  Gradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca(2+)](i) in PGF(2α) (10 μM)-contracted arteries whereas no fall in [Ca(2+)](i) was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and K(Ca)1.1 inhibited hypoxia-induced dilatation in PGF2α -contracted arteries; this inhibition was more marked in the presence of the K(v)7 channel blockers, XE991 and linopirdine, while a K(V)7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H₂S- and adenosine-induced vasodilatation. PCR revealed the expression of K(V)7.1, K(V)7.4, K(V)7.5 and K(Ca)1.1 channels, and K(Ca)1.1, K(V)7.4 and K(V)7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions.
  
  
  CONCLUSIONS
  The K(V)7.4 and K(V)7.5 channels, which we identified in the coronary arteries, appear to have a major role in hypoxia-induced vasodilatation. The voltage clamp results further support the involvement of K(V)7 channels in this vasodilatation. Activation of these K(V)7 channels may be induced by H₂S and adenosine.
authors.affiliation: Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, University of Aarhus, Aarhus, Denmark.
authors.forename: E R
authors.initials: ER
authors.lastname: Hedegaard
authors.forename: B D
authors.initials: BD
authors.lastname: Nielsen
authors.forename: A
authors.initials: A
authors.lastname: Kun
authors.forename: A D
authors.initials: AD
authors.lastname: Hughes
authors.forename: C
authors.initials: C
authors.lastname: Krøigaard
authors.forename: S
authors.initials: S
authors.lastname: Mogensen
authors.forename: V V
authors.initials: VV
authors.lastname: Matchkov
authors.forename: O
authors.initials: O
authors.lastname: Fröbert
authors.forename: U
authors.initials: U
authors.lastname: Simonsen
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051656:KCNQ Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015398:Signal Transduction; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D051656:KCNQ Potassium Channels; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D000241:Adenosine; D010100:Oxygen; D006862:Hydrogen Sulfide
keywords: H2S; KV7; adenosine; calcium; coronary; hypoxia; potassium channels; vasodilatation